This invention relates to new and useful compositions containing an effective anti-inflammatory concentration of piroxicam in a dermatologically acceptable gel base. Clear compositions can be made and are preferred.
Although piroxicam is very active as an anti-inflammatory drug, it is sparingly soluble in water and is not oil soluble. To get the maximum efficacy that piroxicam can provide, the drug should be in solution.
When piroxicam is suspended in conventional dermatological bases, such as ointments or creams, it is poorly absorbed through the skin and does not afford maximum therapeutic efficacy. Alcoholic solutions of piroxicam would seem to offer a possible solution. However, when alcoholic solutions of piroxicam are applied to the skin, the alcohol evaporates off causing the piroxicam to precipitate onto the skin surface. The piroxicam precipitate is not absorbed through the skin.
In the presence of water, piroxicam converts to a hydrate. Since the hydrate is less soluble than piroxicam itself, it gradually crystallizes out. This not only reduces the penetration of piroxicam through the skin, but also impairs the stability of the product as well as its ability to form a film on the skin.
A similar problem occurs when a piroxicam containing gel is applied directly to sweating skin. The polymer gel-forming agent in the product salts out causing the gel to agglomerate on the skin instead of forming a continuous film. This is cosmetically inelegant. The agglomerates have an unpleasant feel. Moreover, piroxicam contained in such agglomerates is not readily bio-available and efficacy of the product is greatly reduced. U.S. Pat. No. 4,678,666 discloses a piroxicam gel containing lower alkanol, water, carboxyvinyl polymer, polyhydric alcohol, alkanolamine and a film-forming agent. Patentees claim that their composition has excellent skin-permeability and none of the defects heretofore described. They employ alkanolamines such as monoalkanolamine, dialkanolamine and trialkanolamine to solubilize the piroxicam. Patentees also disclose that hydroxypropylcellulose was ineffective when combined with their piroxicam-ethanolamine solubilized compositions.
Although U.S. Pat. No. 4,678,666 teaches that alkanolamines are highly effective in increasing the solubility of piroxicam, the present inventor has found that clear-gel piroxicam containing formulations can not be produced when triethanolamine is employed as a solublizer and less than 30% by weight of water is present in the formulation. The product that results turns hazy and eventually forms two layers. Consequently, the gel compositions of U.S. Pat. No. 4678666, particularly those employing triethanolamine as a solubilizer, are less than satisfactory when such compositions contain less than 30% by weight of water.
The present inventor has discovered a new piroxicam solubilizer. The new solubilizer, tetrahydroxypropyl ethylenediamine, is not an alkanolamine as taught by U.S. Pat. No. 4678666. Moreover, it is superior to alkanolamines with respect to color, clarity and gel formation. Its use enables one skilled in the art to prepare stable piroxicam clear gel formulations containing less than 30% by weight of water.
Surprisingly, contrary to the teaching of U.S. Pat. No. 4,678,666 with compositions containing piroxicam solubilized by tetrahydroxypropyl ethylenediamine in accordance with the present invention, hydroxypropylcellulose, a material disclosed by Patentees in U.S. Pat. No. 4,678,666 to be unsatisfactory, is not only effective, it is preferred.